The Role of PPAR𝛾 Receptors and Leukotriene B4 Receptors in Mediating the Effects of LY293111 in Pancreatic Cancer

Pancreatic cancer is a devastating disease in which current therapies are inadequate. Separate lines of research have identified the 5-lipoxygenase/leukotriene B4 receptor pathway and the PPAR𝛾 pathway as potential targets for prevention or treatment of this disease. LY293111 was originally designed...

Full description

Saved in:
Bibliographic Details
Main Authors: Thomas E. Adrian, Rene Hennig, Helmut Friess, Xianzhong Ding
Format: Article
Language:English
Published: Wiley 2008-01-01
Series:PPAR Research
Online Access:http://dx.doi.org/10.1155/2008/827096
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Pancreatic cancer is a devastating disease in which current therapies are inadequate. Separate lines of research have identified the 5-lipoxygenase/leukotriene B4 receptor pathway and the PPAR𝛾 pathway as potential targets for prevention or treatment of this disease. LY293111 was originally designed as a potent leukotriene B4 receptor antagonist for treatment of inflammatory conditions. LY293111 was also known to have inhibitory effects on 5-lipoxygenase, which is upstream of the production of leukotrienes. LY293111 was shown to have potent anticancer effects in pancreatic cancer and several other solid malignancies, where it caused cell cycle arrest and marked apoptosis. Subsequently, it came to light that LY293111 exhibited PPAR𝛾 agonist activity in addition to its effects on the 5-lipoxygenase pathway. This raises the question of which of the two targets is of greatest importance with regard to the anticancer effects of this agent. The evidence to date is not conclusive, but suggests that the effects of LY293111 may be mediated by both LTB4 receptors and PPAR𝛾.
ISSN:1687-4757
1687-4765